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William C Gordon, Bokkyoo Jun, Nicolas G Bazan; Very long chain polyunsaturated fatty acids (VLC-PUFAs) in cone- and rod-rich regions of the human retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1734.
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© ARVO (1962-2015); The Authors (2016-present)
Docosahexaenoic acid (22:6) is concentrated in photoreceptors, located at the sn-2 position on PC VLC-PUFAs, necessary for vision, and is released from phospholipids during stress to form neuroprotective pro-homeostatic mediators that include neuroprotection D1. In AdipoR1 knockout mice 22:6 uptake/retention is inhibited, PC-containing VLC-PUFAs are greatly reduced, and photoreceptors degenerate, displaying a flecked retina (Rice et al, Nature Com, 2015). Since the onset of retinal degenerations are observed at specific retinal locations (cone-rich macula vs rod-rich periphery), we asked if the VLC-PUFA profile changed in different retinal areas.
Normal human eyes were obtained from NDRI and punches taken of the macula and periphery. VLC-PUFAs were characterized by LC/MS/MS and the data normalized by internal standard (deuterated arachidonic acid) or by percent of total species. Phosphatidylcholine (PC) species were also standardized against PC(44:0) and (28:0). PC-containing VLC-PUFAs have 22:6 esterified at the sn-2 position. MALDI lipid profiles of cone- and rod-rich regions were obtained and compared to determine relative abundance of lipid species.
PC sn-1 fatty acids (FAs) from 22 carbons (C) to 32C were in low abundance, 32 and 34C were abundant, 36C were less abundant, and 38C very scarce. PC(40:8; 20:4/20/4) was uniformly distributed among cone- and rod-rich regions, but PC(44:12; 22:6/22:6) was more prevalent in peripheral retina. Total VLC-PUFA-containing PCs were also more abundant peripherally, however, 58C PCs were evenly distributed. Comparisons of macular and peripheral spectra by MALDI imaging revealed significant differences in PC distribution. For example, 34:6, 36:9, and 46:10 were more prevalent in cone-rich retina; 36:4, 38:4, 56:10 were more abundant in the rod-rich region.
Synthesis of 32 and 34C VLC-PUFAs results in few 24-32C FAs, indicating shorter chain FAs are steps in long chain synthesis; 32C and 34C VLC-PUFA abundance, with some 36C and 38C, thus indicate end points. PC spectra from rod-rich areas are distinctly different from the cone-rich region, implying a difference in molecular makeup of each photoreceptor type, and suggesting that differences in photoreceptor lipid profiles may contribute to susceptibility of disease-inducing cellular and molecular events.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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